J. De Seze

Immunosuppressive therapy is more effective than interferon in neuromyelitis optica

To determine long-term treatment (LTT) of neuromyelitis optica (NMO), we retrospectively reviewed therapies of 26 patients with NMO followed in five French neurological departments. To assess LTT efficacy, the probability of relapse free after LTT was analysed. Patients were divided into two groups according to the first treatment receiving interferon beta (IFN Group, seven patients) or immunosuppressants (IS Group, 19 patients). The probability of relapse was significantly lower in the IS Group (P = 0.0007). From our results, interferon beta is not recommended, and one of the best current therapeutic options for NMO appears to be immunosuppressants. Multiple Sclerosis 2007; 13: 256–259. http://msj.sagepub.com

Devic's neuromyelitis optica: clinical, laboratory, MRI and outcome profile

Devics neuromyelitis optica (NMO) associates optic neuritis and myelitis without any other neurological signs. Many patients with NMO may be diagnosed as having multiple sclerosis (MS), optic neuritis and myelitis being the inaugural symptom in 20% and 5% of MS cases, respectively. The aim of our study was to compare a new NMO cohort with recent studies and to try to determine the place of NMO in the spectrum of MS. We retrospectively studied 13 patients with a complete diagnostic workup for NMO. We compared our data with the most recent studies on NMO and with the criteria proposed by Wingerchuck et al. [Neurology 53 (1999) 1107]. We also determined whether these patients fulfilled the diagnostic criteria for MS. Thirteen patients (10 women and three men, with a mean age of 37.4 years) were included in the study. We found similar results to previously published data, except for an association with vasculitis in 38% of our cases. All but three of the patients fulfilled the clinical criteria for MS and two patients fulfilled both clinical and MRI criteria for MS. However, if we applied more restrictive criteria concerning spinal cord and brain MRI and CSF, none of our NMO patients fulfilled the MS diagnostic criteria. NMO might therefore be differentiated from MS by the application of more stringent criteria. Furthermore, all NMO patients should be investigated for vasculitis, even those with no history of systemic disease.

Neuromyelitis optica in France A multicenter study of 125 patients

Background: There have been few epidemiologic studies on neuromyelitis optica (NMO) and none used the recent 2006 diagnostic criteria. Here we describe the clinical, laboratory, MRI, and disability course of NMO in a French cohort of 125 patients. Methods: We performed an observational, retrospective, multicenter study. Data were collected from September 2007 through August 2008, corresponding to the endpoint of the study. We identified 125 patients fulfilling the 2006 NMO criteria. Selection was made using hospital files and a specific clinical questionnaire for NMO. Results: Mean age at onset was 34.5 years (range 4–66) with a mean disease duration of 10 ± 7.8 years at the endpoint. The patients were mainly (87%) Caucasian, with a female:male ratio of 3:1. In 90% of cases, the association of optic neuritis, longitudinal extensive myelitis, and a Paty-negative initial brain MRI was sufficient to fulfill the supportive criteria. Eighty-eight percent of patients were treated with immunosuppressive therapies. Median delay from onset to Expanded Disability Status Scale (EDSS) score 4 was 7 years; score 6, 10 years; and score 7, 21 years. The first episode of myelitis was immediately followed by an EDSS score ≥4 in 37.3% of cases, and a severe residual visual loss was observed in 22% of patients after the first episode of optic neuritis. Multivariate analysis did not reveal any predictors of a poor evolution other than a high number of MRI brain lesions at diagnosis, which were predictive of a residual visual acuity ≤1/10. Conclusions: Our demographic data provide new data on disability in patients with neuromyelitis optica, most of whom were receiving treatment.

Is Devic's neuromyelitis optica a separate disease? A comparative study with multiple sclerosis.

Devics neuromyelitis optica (NMO) associates optic neuritis and myelopathy without other neurological signs. Many patients with NMO may be diagnosed as having multiple sclerosis (MS). However, there have been no previous studies comparing these two patho logies and it is still unclear if NMO is a separate entity or a subtype of MS. In the present study, we compared a series of NMO patients with a series of MS patients for whom optic neuritis or myelopathy was the presenting symptom, in order to determine the place of NMO in the spectrum of MS. We retrospectively studied 30 patients diagnosed with NMO and we compared these patients with 50 consecutive MS cases revealed by optic neuritis or acute myelopathy. MS patients were only included if a relapse occurred demonstrating time and space dissemination. We compared the two groups in terms of clinical presentatio n, laboratory findings (MRI and C SF) and clinical outcome. NMO patients were older and more frequently women than MS patients but the difference was not significant. C SF and MRI data were clearly different: oligoclonal bands (O C B) were found in 23% of NMO cases and 88% of MS (P B/0.001), abnormal brain MRI data were observed in 10% of NMO cases and 66% of MS (P B/0.001) and a large spinal cord lesion was observed in 67% of NMO cases and 7.4% of MS cases (P B/0.001). C linical outcome was evaluated as more severe in the NMO group (P B/0.001). O n the basis of clinical data, all NMO patients but three had dissemination in time and space. When we included MRI parameters, only two of the NMO patients met criteria for MS and one of the MS patients met criteria for NMO. O ur study demonstrates that NMO and MS should be considered as two different entities. The respective criteria for NMO and MS were able to distinguish these two patho logies but only when MRI data were applied. This finding could have implications for future therapeutic trials.

Idiopathic acute transverse myelitis: Application of the recent diagnostic criteria

Despite an extensive diagnostic workup, some cases of acute transverse myelitis (ATM) remain of unknown etiology and have been referred to as “idiopathic” by the Transverse Myelitis Consortium group. In a retrospective study of 288 patients with ATM, 45 cases (15.6%) met the criteria for idiopathic ATM. The patients formed a relatively homogeneous group in terms of clinical and MRI data, but the prognosis was highly variable.

RELEVANCE OF THE ANTIBODY INDEX TO DIAGNOSE LYME NEUROBORRELIOSIS AMONG SEROPOSITIVE PATIENTS

Background: No consensual criteria exist to diagnose neuroborreliosis. The intrathecal anti-Borrelia antibody index (AI) is a necessary criterion to diagnose neuroborreliosis in Europe, but not in the United States. Previous studies to determine the diagnostic value of the AI found a sensitivity ranging from 55% to 80%. However, these studies included only typical clinical cases of meningitis or meningoradiculitis, and none had a control group with CSF anti-Borrelia antibodies. Methods: We studied a sample of 123 consecutive patients with clinical signs of neurologic involvement and CSF anti-Borrelia antibodies. We determined the AI for all patients and a final diagnosis was made. Patients were then divided into three groups (neuroborreliosis, possible neuroborreliosis, control). Results: Thirty of the 40 patients with neuroborreliosis had a positive AI (AI sensitivity = 75%). Two of the 74 patients with another neurologic diagnosis had a positive AI (AI specificity = 97%). Conclusion: The antibody index has a very good specificity but only moderate sensitivity. Given the lack of consensual criteria for neuroborreliosis and the absence of a “gold standard” diagnostic test, we propose pragmatic diagnostic criteria for neuroborreliosis, namely the presence of four of the following five items: no past history of neuroborreliosis, positive CSF ELISA serology, positive anti-Borrelia antibody index, favorable outcome after specific antibiotic treatment, and no differential diagnosis. These new criteria will need to be tested in a larger, prospective cohort.

Evidence-based guideline: clinical evaluation and treatment of transverse myelitis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

Objective: To assess the evidence for diagnostic tests and therapies for transverse myelitis (TM) and make evidence-based recommendations. Methods: A review of the published literature from 1966 to March 2009 was performed, with evidence-based classification of relevant articles. Recommendations: Level B recommendations: neuromyelitis optica (NMO)–immunoglobulin G (IgG) antibodies should be considered useful to determine TM cause in patients presenting with clinical acute complete transverse myelitis (ACTM) features. The presence of NMO-IgG antibodies (aquaporin-4–specific antibodies) should be considered useful in determining increased TM recurrence risk. Level C recommendations: in suspected TM, distinction between ACTM or acute partial transverse myelitis may be considered useful to determine TM etiology and risk for relapse (more common with APTM). Age and gender may be considered useful to determine etiology in patients presenting with TM syndrome, with spinal infarcts seen more often in older patients and more female than male patients having TM due to multiple sclerosis (MS). Brain MRI characteristics consistent with those of MS may be considered useful to predict conversion to MS after a first partial TM episode. Longer spinal lesions extending over >3 vertebral segments may be considered useful in determining NMO vs MS. CSF examination for cells and oligoclonal bands may be considered useful to determine the cause of the TM syndrome. Plasma exchange may be considered in patients with TM who fail to improve after corticosteroid treatment. Rituximab may be considered in patients with TM due to NMO to decrease the number of relapses. Level U recommendations: there is insufficient evidence to support or refute the efficacy of other TM therapies or the usefulness of ethnicity to determine the cause of a subacute myelopathy. GLOSSARY: ACTM: acute complete transverse myelitis APTM: acute partial transverse myelitis CI: confidence interval IgG: immunoglobulin G MS: multiple sclerosis NMO: neuromyelitis optica OCB: oligoclonal band TM: transverse myelitisObjective: To assess the evidence for diagnostic tests and therapies for transverse myelitis (TM) and make evidence-based recommendations. Methods: A review of the published literature from 1966 to March 2009 was performed, with evidence-based classification of relevant articles. Recommendations: Level B recommendations: neuromyelitis optica (NMO)–immunoglobulin G (IgG) antibodies should be considered useful to determine TM cause in patients presenting with clinical acute complete transverse myelitis (ACTM) features. The presence of NMO-IgG antibodies (aquaporin-4–specific antibodies) should be considered useful in determining increased TM recurrence risk. Level C recommendations: in suspected TM, distinction between ACTM or acute partial transverse myelitis may be considered useful to determine TM etiology and risk for relapse (more common with APTM). Age and gender may be considered useful to determine etiology in patients presenting with TM syndrome, with spinal infarcts seen more often in older patients and more female than male patients having TM due to multiple sclerosis (MS). Brain MRI characteristics consistent with those of MS may be considered useful to predict conversion to MS after a first partial TM episode. Longer spinal lesions extending over 3 vertebral segments may be considered useful in determining NMO vs MS. CSF examination for cells and oligoclonal bands may be considered useful to determine the cause of the TM syndrome. Plasma exchange may be considered in patients with TM who fail to improve after corticosteroid treatment. Rituximab may be considered in patients with TM due to NMO to decrease the number of relapses. Level U recommendations: there is insufficient evidence to support or refute the efficacy of other TM therapies or the usefulness of ethnicity to determine the cause of a subacute myelopathy. Neurology 2011;77:2128–2134

Unexpected multiple sclerosis: follow-up of 30 patients with magnetic resonance imaging and clinical conversion profile

The concept of preclinical multiple sclerosis is now well recognised, and a diagnosis of silent brain T2 lesions is frequent because of the ease of performing MRI. Nevertheless, patients with incidental brain MRI fulfilling Barkhof– Tintoré criteria are more rare. We report a descriptive retrospective study of clinical and 5 year MRI follow-up in patients with subclinical demyelinating lesions fulfilling MRI Barkhof–Tintoré criteria with a normal neurological examination. 30 patients were identified and the first brain MRI was performed for various medical events: headaches (n = 14), migraine with (n = 2) or without (n = 4) aura, craniocerebral trauma (n = 3), depression (n = 3), dysmenorrhoea (n = 2), epilepsy (n = 1) and cognitive changes (n = 1). Mean time for the second brain MRI was 6 months (range 3–30). 23 patients had temporospatial dissemination (eight with gadolinium enhancement). 11 patients had clinical conversion: optic neuritis (n = 5), brainstem (n = 3), sensitive symptoms (n = 2) and cognitive deterioration (n = 1). Eight (72%) already had criteria of dissemination to space and time before the clinical event. Mean time between the first brain MRI and clinically isolated syndrome (CIS) was 2.3 years. To our knowledge, this is the first cohort of CIS with preclinical follow-up. Early treatment should be discussed in view of the predictive value on conversion of the MRI burden of the disease.

Low levels of the vascular endothelial growth factor in CSF from early ALS patients

Deletion of the hypoxia-response element in the vascular endothelial growth factor (VEGF) promoter causes motor neuron degeneration in a mouse model. “At-risk” haplotypes with low circulating VEGF levels have been demonstrated in humans. Here the authors report low VEGF levels in the CSF of ALS patients during their first year of the disease, independently of VEGF promoter polymorphism. This finding early in ALS patients suggests a possible role for VEGF gene regulation in the pathogenesis of ALS.

Is neuromyelitis optica associated with human leukocyte antigen

Background To establish whether or not multiple sclerosis (MS) and neuromyelitis optica (NMO) are different pathological entities, we wondered whether MS patients and NMO patients share the same pattern of human leukocyte antigen (HLA) predisposition. Objective To study a putative association between susceptibility to NMO and HLA class I or class II loci in Caucasians. Methods A total of 39 unrelated Caucasian patients with NMO and six patients at a high risk of converting to NMO were studied. DNA genotyping of HLA class I and class II loci was assessed and allelic frequencies were reported at a high-resolution level. A case-control study by comparing the allelic distribution in the NMO patients with that of a French Caucasian MS group and a French Caucasian healthy group was carried out. Results The frequencies of HLA-DQA1, DQB1, and HLA-DRB1 DR2 alleles in the NMO group were intermediate between the healthy control group and the MS group. The DPB1*0501 allele was not increased in the NMO group compared with the healthy control group. The distribution of HLA-DRB1 allele enabled to distinguish between NMO-IgG-positive patients and healthy controls (P = 0.01). NMO-IgG-negative patients presented an HLA II pattern closer to that of the MS group (P = 0.01). Conclusion In contrast to the reported results in Asian opticospinal MS, we found no association between the DPB1*0501 allele and NMO in our Caucasian patients. Moreover, we suggest that NMO-IgG-positive patients could represent a distinct NMO group in terms of their genetic susceptibility.